Since its introduction in 1949 by Cade, lithium is now widely used in the treatment and prophylaxis of manic-depressive psychosis. Clinical studies, however, have shown in increasing numbers that prolonged lithium treatment may be associated with a wide range of endocrine and metabolic side-effects and adverse reactions. Notably, a perusal of the existing literature on lithium reveals, rather strikingly, that very little is known as to what effects lithium has on fertility in women. This is rather surprising since there is evidence to suggest that women are more likely than men to develop mania and depression and that the maximum risk for these affective states is during the reproductive years in women. Another important area that has not received much attention is whether lithium treatment in women during pregnancy or nursing affects the reproductive function in the offsprings born to lithium-treated mothers. Whether intrauterine exposure to lithium affects the development and growth of other organ systems also remains largely unknown. The central aim of the proposed research, therefore, is to address to these important aspects of lithium's action. To achieve these goals, the C57BL/6 mouse will be utilized as a suitable model. To examine the effects of lithium on fertility, the proestrous surges in LH and FSH will be selected as an important criterion since the preovulatory suges in FSH and LH are known to be essential for ovulation and the formation of a normal corpus luteum. To evaluate the effects of lithium, administered during pregnancy or nursing, on the reproductive function in the young, various evaluative criteria (such as age of vaginal opening, initiation of and regularity in estrous cycle, plasma levels of FSH and LH in proestrous for the female offsprings, and plasma levels of testosterone (T) for male pups) will be employed. Levels of LH, FSH and T will be measured by RIA. Evaluation of ovulation will be done by ovarian histology and by counting the number of ova from oviductal flushing. Attempts will also be made to examine whether exposure to lithium in utero affects organ weights and/or produces gross morphological or pathological changes in some important organs in the neonates or in the adult stage. It is believed that valuable information will be obtained from our proposed studies. Conceivably, our results may have important clinicial significance.